Figure 2

Clonal structure of tumor and normal cells. (A) Clonal structure of tumor and normal cells (rows) profiled in a heat map by nonsynonymous mutant genes (columns). Based on sequencing data and taking uncertainty in allele observation caused by allele dropout and binomial noise, the likelihood ratio for being not mutant was calculated for every gene in every cell. A profiling color of red meant a gene of likely mutant in the cell, while blue meant not mutant. Three major cell subclones were identified in tumor cells: 1) Clone A, with concordant mutant genes in Group I; 2) Clone B, with concordant mutant genes in Group I and Group III; 3) Clone C, with concordant mutant genes in Group I and Group II. Normal cells were clustered together (Clone N), free of mutations in all the three gene groups. (B) Somatic mutant allele frequency of certain genes in cancer tissue were detected by mass spectrometry. We detected 27 genes, in the three subclones incancer tissue by mass spectrometry (MassARRAY Analyzer) genotyping. (C) Concurrent and exclusive mutation analysis of mutant genes in tumoral cell population. Concurrent and exclusive mutation analysis was performed with two Perl packages [41, 42]. The result was a concurrent and exclusive p-value between each two selected genes, indicated as depths of color. Note: a p-value ≥0.3 was indicated as white.